Drug-induced phospholipidosis is a lysosomal storage disorder characterized by the excess accumulation of phospholipids in cells and tissues. Phospholipidosis is a common finding in toxicity studies of cationic amphiphilic drugs (CADs) in both animals and humans and has become a significant regulatory concern. Major concerns for regulatory agencies are drug-induced phospholipidosis of the liver, kidneys, muscle, heart, and lung tissues, which could contribute to the adverse effects of drugs in these organs. The morphological effects of drug-induced phospholipidosis in tissues resemble the whorled myelin figures in the tissues of patients with Niemann-Pick Type C (NPC) disease. NPC and other inherited lysosomal storage disorders result in the harmful accumulation of lipid materials (e.g., lipids, glycolipids, lipoproteins) in the body's cells and tissues. Over time, excessive storage of the lipid materials causes permanent cellular and tissue damage, particularly in the brain, peripheral nervous system, liver, spleen, and bone marrow.
Drug-induced phospholipidosis cannot currently be determined non-invasively. There is a need for readily accessible biomarkers to determine the onset and time course of phospholipidosis in preclinical and clinical studies and to explore the links between phospholipidosis and the toxicities of drugs.